Preventing Venous Thromboembolism in Hospitalized Patients With Cancer

Improving Compliance With Clinical Practice Guidelines

Alexandra Brown


Am J Health Syst Pharm. 2012;69(6):469-481. 

In This Article

Role of the Pharmacist

Apart from the obvious desire to improve outcomes for patients, there is now further incentive to improve VTE prophylaxis rates due to the initiatives of various organizations whose policies affect reimbursement. The Centers for Medicare and Medicaid Services (CMS) has proposed regulations that give hospitals financial incentives to improve the quality of care of patients.[68] According to this proposal, hospitals would be made to bear the increased costs of treating hospital-acquired conditions that could have been prevented by adherence to evidence-based guidelines.[69] A number of reporting measures—known as the Reporting Hospital Quality Data for Annual Payment (RHQDAP—include prophylaxis of VTE for surgical patients, and it is possible that these quality data could eventually be expanded to other types of patients. These measures determine the CMS payment rates to hospitals, with higher rates reserved for hospitals that are successful in reporting designated quality measures. CMS has also proposed the "never event," a preventable medical error that results in serious consequences for the patient, such as VTE after knee or hip replacement.[69] Hospitals will no longer receive payment for these hospital-acquired conditions. These provisions are not surprising, considering that VTE remains the most preventable cause of hospital death.[6]

Organizations such as the Joint Commission[70] and the Surgical Care Improvement Project (SCIP)[71] also provide strong incentives for improving VTE prophylaxis practices. The Joint Commission collaborated with the National Quality Forum to develop standard metrics to assess VTE prophylaxis practices in hospitals.[70] The VTE standards include assessing the number of eligible patients who do not receive VTE prophylaxis on admission, discovering the reasons for failure to prescribe thromboprophylaxis at admission or perioperatively, and determining the percentage of patients with confirmed VTE during hospitalization who did not receive prophylaxis between hospital admission and the day before the VTE diagnostic test. Similarly, SCIP is a partnership of organizations whose objectives are to reduce surgical morbidity and mortality. SCIP's outcome measures for VTE, known as VTE 1 and VTE 2, quantify the appropriate ordering and dispensing of VTE prophylaxis 24 hours before and after surgery. CMS currently includes these measures as part of the RHQDAP and has proposed applying them to nonsurgical patients in subsequent years.[71]

Pharmacist interventions can help to improve a health system's compliance with required quality measures. There are several stages in the continuum of care for hospitalized patients during which interventions can be made by pharmacists to ensure VTE prophylaxis: assessment of risk, recommendations for therapy, monitoring of therapy, and reinforcement at the patient level (patient education and counseling). Assessment of risk and recommendations for therapy are effectively addressed with an admission protocol or with protocols designed to cover all patients at various stages of their hospitalization. Pharmacists could be an important part of the team in designing such protocols because of their clinical knowledge and their oversight of patient care as patients are transferred from one service to another during the total hospital stay. ACCP makes very clear that there should be a formal strategy in place to ensure the implementation of VTE prophylaxis.[54] There is consensus that casual dissemination of guidelines does not result in improvements in clinicians' performance. Instead, an effective strategy is more likely to be one that is active (e.g., workshop), is multifaceted, and employs an iterative process of audit and feedback.[72] Decision-support tools, such as risk- assessment models, computer-based reminders that are integrated into computerized order-entry systems, and alerts accompanied by recommendations, have been shown to be effective.[12] An AHRQ publication provides detailed suggestions for initiating a VTE protocol and tracking its implementation.[5] Many VTE risk-assessment tools can be found, and at least one has been tested and validated specifically for patients with cancer.[73] Khorana et al.[73] have published a risk-assessment model for chemotherapy-associated VTE that includes the following factors:

  • Site of cancer (very high risk [stomach, pancreas] and high risk [lung, lymphoma, gynecological, bladder, testicular]),

  • Prechemotherapy platelet count of >350,000/μL,

  • Hemoglobin concentration of <10 g/dL or use of red cell growth factors,

  • Prechemotherapy leukocyte count of >11,000/μL, and

  • Body mass index of ≥35 kg/m2.

In this model, each factor accrues a score of 1 point, except for very-high-risk cancer sites, which score 2 points. The final score determines the risk category as follows: low (0 point), intermediate (1–2 points), and high (≥3 points). In the validation study, patients in the high-risk category had an almost 7% risk of developing VTE over a 2.5-month period, whereas those in the low- and intermediate-risk groups had risks of only 0.3% and 2%, respectively. The authors concluded that this model can be used for risk assessment as well as to select appropriate patients for clinical thromboprophylaxis trials.

Once VTE prophylaxis is initiated, pharmacists can have a critical role in monitoring therapy. Medical patients receiving prophylactic doses of unfractionated heparin usually do not need activated partial thromboplastin time measurements, but hemoglobin level, hematocrit value, and platelet count should be checked every 2–3 days for the first two weeks and then every two weeks, according to NCCN.[74] Patients receiving unfractionated heparin or an LMWH may become thrombocytopenic or develop heparin-induced thrombocytopenia (HIT). HIT is suspected if the platelet count falls by 50% or more between days 4 and 14 after the initiation of heparin or if a thrombotic event occurs during heparin therapy.[75] Thus, patients receiving heparin must have their platelet counts monitored and be checked for symptoms of thrombosis. ACCP guidelines suggest that surgical patients on prophylactic unfractionated heparin should be monitored every-other-day on postoperative days 4–14 and every 2–3 days if on an LMWH.[54] Medical patients on prophylactic-dose unfractionated heparin, or those on an LMWH after receiving unfractionated heparin, should be monitored every 2–3 days from days 4 to 14. Medical patients who are receiving only an LMWH do not need routine platelet counts. Anticoagulation for a patient with HIT is achieved with a direct thrombin inhibitor, such as argatroban or lepirudin, or fondaparinux, with the introduction of warfarin when platelets have recovered (>100,000–150,000 cells/μL). Pharmacists should be aware that argatroban is cleared hepatically and lepirudin and fondaparinux are cleared renally; therefore, the choice of agent is patient specific. The INR and platelet count need to be tracked in patients receiving these drugs.

Limited information exists on specific dosages for prophylaxis in special populations (obese, renal impairment, and geriatric). Factor Xa inhibition may need to be measured in obese patients (>150 kg) who receive anticoagulation therapy with an LMWH or fondaparinux for an extended period, since dosing guidelines may be unreliable in these patients.[53] Similarly, patients with low body weight or decreased renal function may need close monitoring of bleeding or anti-Xa measurement to rule out drug accumulation. Most pharmacokinetic data in renal insufficiency have been collected with enoxaparin, and limited data suggest there is less bioaccumulation with dalteparin and tinzaparin.[76] Initial doses of enoxaparin must be decreased in patients with renal disease; however, since tinzaparin and dalteparin may be less likely to bioaccumulate in the presence of renal dysfunction, dosage adjustment may not be required for prophylactic doses with these two drugs.[52] ACCP recommends the use of anticoagulants that do not bioaccumulate in the presence of renal dysfunction, such as dalteparin, in patients who are elderly, have diabetes mellitus, or are at high risk for bleeding and that anticoagulant effects be monitored.[54] NCCN guidelines discuss the fact that tinzaparin is an LMWH that does not accumulate with renal insufficiency; however, the manufacturer recommends caution when creatinine clearance is <30 mL/min and the use an alternative drug for VTE treatment in elderly patients with renal dysfunction.

Monitoring is also required for patients receiving erythropoiesis-stimulating agents (ESAs), which may increase tumor growth, mortality, and VTE risk.[77] These risks appear to be increased when the hemoglobin concentration exceeds 12 g/dL or when patients achieve more than a 1-g/dL increase in hemoglobin concentration in 14 days. An increased number of vascular events has been reported when the hematocrit target is high (42% ± 3%). Hemoglobin levels should also be monitored to decrease the risks of hypertension and seizures.[77] It is mandatory for hospitals and clinicians to be enrolled in the risk evaluation and mitigation strategy (REMS) that has been developed by Amgen, the manufacturer of three ESAs (Epogen, Procrit, and Aranesp).[77] The program, called the ESA APPRISE (Assisting Providers and Cancer Patients with Risk Information for the Safe Use of ESAs) Oncology Program, requires training for hospital staff and health care professionals to ensure understanding of the risks of ESAs and the appropriateness of and contraindications to therapy.

Another important role for the pharmacist is to track patients who are not receiving pharmacologic prophylaxis due to bleeding risk factors, as these patients need continual reassessment of their risk level, with thromboprophylaxis initiated when appropriate and feasible. Finally, to ensure that anticoagulation compliance is complete, when parenteral anticoagulants are withheld before procedures, pharmacists should ensure that they are restarted when patients are transferred to recovery units or another service.

Patient education and counseling are usually provided for those who will be receiving anticoagulants as outpatients. However, it is also appropriate to counsel hospitalized patients so that they are aware of symptoms of VTE and adverse effects of anticoagulants. Because many patients will continue with therapy after hospital discharge, this is an opportunity to introduce and reinforce complex information during the hospital stay. A large number of cancer patients are unaware of the increased risk of thromboembolism (53% in one study),[78] but patients who are well aware of the risk may be more likely to use prophylaxis and accept the negative aspects of therapy, such as daily injections or frequent monitoring. At the same time, patients who are receiving ESAs will need to be counseled according to the REMS and provided with the accompanying medication guide, as discussed above. Pharmacists can help these patients to better understand the risks and benefits of ESA therapy.


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